Alterations in monoaminergic neuron function have been implicated in psychosis and affective disorders. An understanding of monoamine neuron function may shed light on the neural basis, as well as provide insight for treatment, of these serious diseases. Our goal is to study monoamine neuron function by studying mechanisms of action of psychoactive drugs using single cell recording and microiontophoretic techniques in the rat. Based upon research findings in our laboratories, we wish to pursue four major topics. First, we have found that the d- and 1-isomers of amphetamine (AMP) have differential effects in reducing the firing rates of substantia nigra (nucleus A9) and ventral tegmental area (nucleus A10) dopamine (DA) neurons. d-AMP has equipotent effects on A9 and A10 neurons, however; 1-AMP is relatively impotent in influencing A9 impulse flow, but it is quite potent in influencing A10 impulse flow. We wish to determine why these AMP isomers have differential effects on these two DA nuclei. Second, AMP and non-AMP (e.g. amfonelic acid) CNS stimulants influence DA and norepinephrine (NE) neurons differently. We wish to further study the mechanisms of action of non-AMP CNS stimulants on DA and NE neurons. Third, biochemical research from our laboratories suggests a function for the DA storage granule is the regulation of DA synthesis. We with to determine whether it also functions to regulate DA impulse flow. Finally, chronic antidepressant drug treatment produces subsensitive NE receptors and supersensitive serotonin (5-HT) receptors. We wish to study whether electroconvulsant shock treatment, also an antidepressant therapy, produces similar changes in NE and 5-HT receptor sensitivities, and whether the changes in receptor sensitivity are due to direct effects on the receptors or effects mediated pre- or transynaptically.